Does Immunotherapy for Lung Cancer Work? | MyLungCancerTeam

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Does Immunotherapy for Lung Cancer Work?

Medically reviewed by Todd Gersten, M.D.
Written by Emily Wagner, M.S.
Posted on February 24, 2022

Recent advancements in cancer treatment use specialized antibodies that activate the immune system to shrink and kill tumors. Antibodies are proteins created by the immune system. They attach to other proteins, called antigens, which are seen as harmful or foreign to the body. Once antibodies are attached to antigens, they can trigger other parts of the immune system to act.

The type of antibodies used in cancer treatment are called monoclonal antibodies. They’re designed by scientists to target a specific antigen, like a protein found on cancer cells. Once an antibody is designed in the lab, it can be duplicated many times and used to treat diseases.

Monoclonal antibodies are a kind of immunotherapy, which is “a type of therapy that uses substances to stimulate or suppress the immune system,” according to the U.S. National Cancer Institute. Vaccines are also considered a type of immunotherapy.

The U.S. Food and Drug Administration (FDA) has approved several immunotherapies to treat many different types of cancer, including colorectal, breast, kidney, and lung cancer.

Why Is Immunotherapy Important for Treating Lung Cancer?

Immunotherapy is a relatively new way of treating cancer. The first FDA-approved lung cancer immunotherapy was Opdivo (nivolumab), approved in 2015. Nivolumab was originally authorized for treating advanced-stage melanoma (a type of skin cancer), but it was also found to be effective in treating lung cancer. Specifically, it was used to treat people whose cancer had progressed during or after chemotherapy.

Before the approval of immunotherapies, doctors used many types of conventional treatment options to treat lung cancer. These include chemotherapy, radiation, and targeted therapies. However, over time, cancers can become resistant to the effects of treatment and continue to grow. This is especially the case with chemotherapy and targeted therapy; if tumor cells acquire new genetic mutations, previously effective drugs may no longer affect them.

Immunotherapy can be used alone or in combination with these traditional treatments to enhance their effects. Since 2015, several other immunotherapies have been approved for treating lung cancer.

How Does Immunotherapy Work?

Immunotherapy uses your body’s own natural defense, the immune system, to fight cancer. Normally, your immune system is scanning your body for infections and cancer cells (known as immune surveillance); if it finds anything abnormal, it will try to kill it before it can grow.

However, some tumor cells can evade the immune system, and they can continue to grow and form tumors (known as immune escape). The immune system has natural checks and balances in place so that it can turn itself on and off. For example, during an infection, the immune system will create inflammation and bring other immune cells in to fight it. Once the infection is cleared, the immune system can turn itself off so that it does not cause further damage to healthy cells and tissues.

Tumor cells have learned to mimic this response of turning the immune system off, which lets them hide from immune cells. They do this by expressing a special protein on their surface called PD-L1. This protein interacts with PD-1 found on a type of immune cells known as T cells. When PD-1 and PD-L1 bind together, the T cell is shut off and thus can’t create an immune response. This is called an immune checkpoint.

Monoclonal antibodies have been designed to bind to either PD-1 or PD-L1, which stops them from interacting. This prevents the T cells from being shut off, so they can continue making immune responses and causing inflammation. This inflammation brings in other immune cells that will attack and kill the tumor cells. These immunotherapies are known as immune checkpoint inhibitors.

Immunotherapies Used To Treat Lung Cancer

Immunotherapies used to treat lung cancer can be broken down by the protein they bind to. The most common are PD-1/PD-L1 inhibitors, but there are others.

PD-1 Inhibitors

PD-1 inhibitors include:

  • Keytruda (pembrolizumab)
  • Libtayo (cemiplimab)
  • Opdivo (nivolumab)

PD-L1 Inhibitors

PD-L1 inhibitors include:

  • Imfinzi (durvalumab)
  • Tecentriq (atezolizumab)

CTLA-4 Inhibitor

CTLA-4 is another immune checkpoint found on T cells. When this binds to the protein B7 found on tumor cells, it shuts down the T cell and prevents it from creating an immune response.

Yervoy (ipilimumab) is a CTLA-4 inhibitor that blocks the interaction between CTLA-4 and B7. This leaves the T cell active, so it can activate the immune system to kill the tumor cells.

When Are Immunotherapies Used To Treat Lung Cancer?

Immunotherapies are mainly used to treat lung cancer in its advanced stages. This means that the cancer has spread to more than one location in the body and cannot be easily treated with surgery and/or radiation.

Your tumor may be tested for levels of T cells in and around the tumor. It may also be tested for the presence of PD-L1 on the tumor surface. Immunotherapies tend to work best in tumors with lots of T cells (so that they can interact with the tumor cells and kill them).

Advanced Non-Small Cell Lung Cancer

Non-small cell lung cancer (NSCLC) is classified using different lung cancer staging systems. NSCLC staging begins at stage 0 and extends through stage 4 (the most advanced). Roman numerals are sometimes used for stage numbers. Additionally, numbers and letters sometimes provide a little more information about the condition.

Different types of immunotherapy are used for different stages of NSCLC.

Stage 3A

Immunotherapy is used if surgery, chemotherapy, and/or radiation cannot be used because the person is not healthy enough. Keytruda or Libtayo can be used as a first-line treatment.

Stage 3B

Imfinzi can be given to people who have stable cancer after chemotherapy/radiation to help keep it under control. For people who are not healthy enough to undergo surgery, chemotherapy, or radiation, Libtayo or Keytruda can be given.

Stage 4B

For stage 4B cancer that has spread to multiple sites in the body, there are a few options for immunotherapy treatment:

  • Tecentriq, Libtayo, or Keytruda alone
  • Opdivo and Yervoy, potentially in combination with chemotherapy
  • Keytruda or Tecentriq, in combination with chemotherapy

Advanced Stage Small Cell Lung Cancer

Extensive stage SCLC cannot be treated with surgery or radiation therapy because it has spread too much throughout the body. In these situations, systemic (whole-body) therapies are used for first-line treatments; these include chemotherapy and immunotherapy.

Tecentriq or Imfinzi can be combined with the chemotherapies etoposide and platinum-based drugs (such as carboplatin or cisplatin).

Immunotherapy Clinical Trials for Lung Cancer

Hundreds of clinical trials have studied how well immunotherapy works for treating lung cancer. For many years, platinum-based chemotherapies were used to treat advanced NSCLC.

In 2016, a clinical trial showed that immunotherapy, specifically Keytruda, improved overall survival in people who had the PD-L1 protein on 50 percent or more of their tumor cells.

Extensive-stage SCLC has also been traditionally treated with platinum-based chemotherapies, but these were not highly effective. Two major clinical trials found that the combination of Tecentriq or Imfinzi with etoposide and platinum-based chemotherapies improved overall survival.

Talk With Others Who Understand

MyLungCancerTeam is the social network for people with lung cancer and their loved ones. On MyLungCancer, more than 5,300 members come together to ask questions, give advice, and share their stories with others who understand life with lung cancer.

Have you had immunotherapy to treat your lung cancer? Share your experience in the comments below, or start a conversation by posting on your Activities page.

References
  1. Monoclonal Antibodies and Their Side Effects — American Cancer Society
  2. Immunotherapy — National Cancer Institute
  3. Immunotherapy — Cleveland Clinic
  4. FDA Approves First Immunotherapy Treatment for Lung Cancer — National Cancer Institute
  5. Immunotherapy in NSCLC: A Promising and Revolutionary Weapon — Advances in Experimental Medicine and Biology
  6. Targeted Cancer Therapies — National Cancer Institute
  7. Immunotherapy for Non-Small Cell Lung Cancer — American Cancer Society
  8. Immune Surveillance of Tumors - The Journal of Clinical Investigation
  9. Rejection and Immune Escape of Tumors — Frontiers
  10. The Diverse Function of PD-1/PD-L Pathway Beyond Cancer — Frontiers in Immunology
  11. Immune Checkpoint Inhibitor — National Cancer Institute
  12. CTLA-4 — National Cancer Institute
  13. Non-Small Cell Lung Cancer Stages — American Cancer Society
  14. Treatment Choices for Non-Small Cell Lung Cancer, by Stage — American Cancer Society
  15. Frontline Immunotherapy for NSCLC — The Tale of the Tail — Nature Reviews Clinical Oncology
  16. Treatment Choices for Small Cell Lung Cancer, by Stage — American Cancer Society
  17. Pembrolizumab Versus Chemotherapy for PD-L1-Positive-Non-Small Cell Lung Cancer — The New England Journal of Medicine
  18. First-Line Atezolizumab Plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer — The New England Journal of Medicine
  19. Durvalumab Plus Platinum-Etoposide Versus Platinum-Etoposide in First-Line Treatment of Extensive-Stage Small-Cell Lung Cancer (CASPIAN): A Randomised, Controlled, Open-Label, Phase 3 Trial — The Lancet
Posted on February 24, 2022
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Todd Gersten, M.D. is a hematologist-oncologist at the Florida Cancer Specialists & Research Institute in Wellington, Florida. Review provided by VeriMed Healthcare Network. Learn more about him here.
Emily Wagner, M.S. holds a Master of Science in biomedical sciences with a focus in pharmacology. She is passionate about immunology, cancer biology, and molecular biology. Learn more about her here.

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